Optimising EEG-fMRI for Localisation of Focal Epilepsy in Children

BACKGROUND: Early surgical intervention in children with drug resistant epilepsy has benefits but requires using tolerable and minimally invasive tests. EEG-fMRI studies have demonstrated good sensitivity for the localization of epileptic focus but a poor yield although the reasons for this have not been systematically addressed. While adults EEG-fMRI studies are performed in the "resting state"; children are commonly sedated however, this has associated risks and potential confounds. In this study, we assessed the impact of the following factors on the tolerability and results of EEG-fMRI in children: viewing a movie inside the scanner; movement; occurrence of interictal epileptiform discharges (IED); scan duration and design efficiency. This work's motivation is to optimize EEG-fMRI parameters to make this test widely available to paediatric population. METHODS: Forty-six children with focal epilepsy and 20 controls (6-18) underwent EEG-fMRI. For two 10 minutes sessions subjects were told to lie still with eyes closed, as it is classically performed in adult studies ("rest sessions"), for another two sessions, subjects watched a child friendly stimulation i.e. movie ("movie sessions"). IED were mapped with EEG-fMRI for each session and across sessions. The resulting maps were classified as concordant/discordant with the presumed epileptogenic focus for each subject. FINDINGS: Movement increased with scan duration, but the movie reduced movement by ~40% when played within the first 20 minutes. There was no effect of movie on the occurrence of IED, nor in the concordance of the test. Ability of EEG-fMRI to map the epileptogenic region was similar for the 20 and 40 minute scan durations. Design efficiency was predictive of concordance. CONCLUSIONS: A child friendly natural stimulus improves the tolerability of EEG-fMRI and reduces in-scanner movement without having an effect on IED occurrence and quality of EEG-fMRI maps. This allowed us to scan children as young as 6 and obtain localising information without sedation. Our data suggest that ~20 minutes is the optimal length of scanning for EEG-fMRI studies in children with frequent IED. The efficiency of the fMRI design derived from spontaneous IED generation is an important factor for producing concordant results

Combined EEG-fMRI and ESI improves localisation of paediatric focal epilepsy

OBJECTIVE: Surgical treatment in epilepsy is effective if the epileptogenic zone (EZ) can be correctly localized and characterized. Here we use simultaneous Electroencephalography-functional MRI (EEG-fMRI) data to derive EEG-fMRI and Electrical Source Imaging (ESI) maps. Their yield and their individual and combined ability to 1) localize the epileptogenic zone and 2) predict seizure outcome was then evaluated. METHODS: Fifty-three children with drug-resistant epilepsy underwent EEG-fMRI. Interictal discharges were mapped using both EEG-fMRI haemodynamic responses and Electrical Source Imaging (ESI). A single localization was derived from each individual test (EEG-fMRI global maxima (GM)/ESI maxima) and from the combination of both maps (EEG-fMRI/ESI spatial intersection). To determine the localisation accuracy and its predictive performance the individual and combined test localisations were compared to the presumed EZ and to the postsurgical outcome. RESULTS: Fifty-two/53 patients had significant maps; 47/53 for EEG-fMRI; 44/53 for ESI; 34/53 had both. The epileptogenic zone was well characterised in 29 patients; 26 had an EEG-fMRI GM localisation which was correct in 11; 22 patients had ESI localisation which was correct in 17; 12 patients had combined EEG-fMRI and ESI which was correct in 11. Seizure outcome following resection was correctly predicted by EEG-fMRI GM in 8/20 patients, by the ESI maxima in 13/16. The combined EEG-fMRI/ESI region entirely predicted outcome in 9/9 patients including 3 with no lesion visible on MRI. INTERPRETATION: EEG-fMRI combined with ESI provides a simple unbiased localisation that may predict surgery better than each individual test including in MRI-negative patients

Combined EEG-fMRI and ESI improves localisation of paediatric focal epilepsy

OBJECTIVE: Surgical treatment in epilepsy is effective if the epileptogenic zone (EZ) can be correctly localized and characterized. Here we use simultaneous Electroencephalography-functional MRI (EEG-fMRI) data to derive EEG-fMRI and Electrical Source Imaging (ESI) maps. Their yield and their individual and combined ability to 1) localize the epileptogenic zone and 2) predict seizure outcome was then evaluated. METHODS: Fifty-three children with drug-resistant epilepsy underwent EEG-fMRI. Interictal discharges were mapped using both EEG-fMRI haemodynamic responses and Electrical Source Imaging (ESI). A single localization was derived from each individual test (EEG-fMRI global maxima (GM)/ESI maxima) and from the combination of both maps (EEG-fMRI/ESI spatial intersection). To determine the localisation accuracy and its predictive performance the individual and combined test localisations were compared to the presumed EZ and to the postsurgical outcome. RESULTS: Fifty-two/53 patients had significant maps; 47/53 for EEG-fMRI; 44/53 for ESI; 34/53 had both. The epileptogenic zone was well characterised in 29 patients; 26 had an EEG-fMRI GM localisation which was correct in 11; 22 patients had ESI localisation which was correct in 17; 12 patients had combined EEG-fMRI and ESI which was correct in 11. Seizure outcome following resection was correctly predicted by EEG-fMRI GM in 8/20 patients, by the ESI maxima in 13/16. The combined EEG-fMRI/ESI region entirely predicted outcome in 9/9 patients including 3 with no lesion visible on MRI. INTERPRETATION: EEG-fMRI combined with ESI provides a simple unbiased localisation that may predict surgery better than each individual test including in MRI-negative patients

Libraries and open society; Popper, Soros and digital information

This paper examines the role of libraries and information services, in promoting the ‘open society’ espoused by Karl Popper and George Soros. After a brief discussion of the nature of an ‘open society’, the paper covers the role played by provision of knowledge and information, of new technology, particularly the Internet, and of critical thinking and digital literacy in the development of this form of society. Conclusions are drawn for the role of libraries and librarians, with seven general principles suggested: • provision of access to a wide variety of sources without ‘negative’ restriction or censorship • provision of ‘positive’ guidance on sources, based on open and objective criteria • a recognition that a ‘free flow of information’ though essential, is not sufficient • a recognition that provision of factual information, while valuable, is not enough • a need for a specific concern for the effect of new ICTs, and the Internet in particular • promotion of critical thinking and digital literacy • a need for explicit consideration of the ethical values of librarie

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

<p>Abstract</p> <p>Background</p> <p>This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.</p> <p>Methods</p> <p>A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.</p> <p>Results</p> <p>Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).</p> <p>Conclusion</p> <p>A prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.</p

Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT). METHODS: Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. RESULTS: Median age was 64 years (range: 30–88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6–86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98%) and 84% (CI 95%, 58–95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18–40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04–32.05, P = 0.045). CONCLUSION: EGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis

Haploinsufficiency of the MLL and TOB2 genes in lymphoid malignancy

There are many different mechanisms by which the promiscuous MLL gene, with a diversity of partners, can be converted into an oncogene. These include translocations, duplications, insertions and deletions all of which have been linked to HOX gene deregulation as the mediator of haematological malignancy

Influence of the matrix on analyte fragmentation in atmospheric pressure MALDI

In this paper, we report the measurement of the degree of analyte fragmentation in AP-MALDI as a function of the matrix and of the laser fluence. The analytes include p-OCH3-benzylpyridinium, three peptides containing the sequence EEPP (which cleave very efficiently at the E-P site), and three deoxynucleosides (dA, dG, and dC), which lose the neutral sugar to give the protonated base. We found that the matrix hardness/softness was consistent when comparing the analytes, with a consensus ranking from hardest to softest: CHCA >> DHB > SA approximate to THAP > ATT > HPA. However, the exact ranking can be fluence-dependent, for example between ATT and HPA. Our goal here was to provide the scientific community with a detailed dataset that can be used to compare with theoretical predictions. We tried to correlate the consensus ranking with different matrix properties: sublimation or decomposition temperature (determined using thermogravimetry), analyte initial velocity, and matrix proton affinity. The best correlation was found with the matrix proton affinity